Magnetic resonance imaging (“MRI”) for medical diagnostics can benefit tremendously from use of contrast agents, which are gadolinium compounds. DOTMA and DOTA are well-studied molecules capable of binding gadolinium ions (Gd3+), forming very stable complexes. Each complex can bind a water molecule and alter its relaxivity and hence be used as a MRI contrast agent. The DOTMA complex is superior.
However, neither DOTMA not DOTA are bifunctional, that is, neither can be linked covalently to another molecule, meaning that they cannot be incorporated into polymers, attached to surfaces, or otherwise modified and targeted to a specific disease. There are a few bifunctional derivatives of DOTA in the literature but they are very tedious to make and even making 10 grams is difficult. The cost of buying such compounds can be thousands of dollars per gram.
The present invention provides a first bifunctional DOTMA analog and a robust synthetic method for preparing this analog. The synthetic method is scalable for readily producing 50-gram, 500 gram or more of the bifunctional DOTMA molecule. Moreover, this same chemistry is also applicable to make a related bifunctional DOTA and DO3A analogs as contrast agents with different properties.